PDF(Pubmed)
Abstract：
Lung cancer is the most common cause of cancer-related deaths worldwide and is caused by multiple factors, including high-fat diet (HFD). CD36, a fatty acid receptor, is closely associated with metabolism-related diseases, including cardiovascular disease and cancer. However, the role of CD36 in HFD-accelerated non-small-cell lung cancer (NSCLC) is unclear. In vivo, we fed C57BL/6J wild-type (WT) and CD36 knockout (CD36-/-) mice normal chow or HFD in the presence or absence of pitavastatin 2 weeks before subcutaneous injection of LLC1 cells. In vitro, A549 and NCI-H520 cells were treated with free fatty acids (FFAs) to mimic HFD situation for exploration the underlying mechanisms. We found that HFD promoted LLC1 tumor growth in vivo and that FFAs increased cell proliferation and migration in A549 and NCI-H520 cells. The enhanced cell or tumor growth was inhibited by the lipid-lowering agent pitavastatin, which reduced lipid accumulation. More importantly, we found that plasma soluble CD36 (sCD36) levels were higher in NSCLC patients than those in healthy ones. Compared to that in WT mice, the proliferation of LLC1 cells in CD36-/- mice was largely suppressed, which was further repressed by pitavastatin in HFD group. At the molecular level, we found that CD36 inhibition, either with pitavastatin or plasmid, reduced proliferation- and migration-related protein expression through the AKT/mTOR pathway. Taken together, we demonstrate that inhibition of CD36 expression by pitavastatin or other inhibitors may be a viable strategy for NSCLC treatment.
摘要：
肺癌是全球癌症相关死亡的最常见原因，由多种因素引起，包括高脂肪饮食（HFD）。CD36，一种脂肪酸受体，与代谢相关的疾病密切相关，包括心血管疾病和癌症。然而,CD36在HFD加速非小细胞肺癌(NSCLC)中的作用尚不清楚.在体内,我们饲喂C57BL/6J野生型（WT）和CD36敲除（CD36-/-）小鼠正常食物或HFD在有或没有匹伐他汀的2周前皮下注射LLC1细胞。体外，用游离脂肪酸(FFA)处理A549和NCI-H520细胞以模拟HFD情况以探索潜在机制。我们发现HFD在体内促进LLC1肿瘤生长，FFA增加A549和NCI-H520细胞的细胞增殖和迁移。降脂药匹伐他汀抑制了增强的细胞或肿瘤生长，减少脂质积累。更重要的是,我们发现,NSCLC患者的血浆可溶性CD36(sCD36)水平高于健康患者.与WT小鼠相比，在CD36-/-小鼠中LLC1细胞的增殖被大大抑制，在HFD组中被匹伐他汀进一步抑制。在分子水平上,我们发现CD36抑制，用匹伐他汀或质粒，通过AKT/mTOR途径降低增殖和迁移相关蛋白的表达。一起来看,我们证明匹伐他汀或其他抑制剂抑制CD36表达可能是NSCLC治疗的可行策略.
